Latest classification of ependymoma in the molecular era and advances in its treatment: a review

1. Taylor MD, Poppleton H, Fuller C, et al. Radial glia cells are candidate stem cells

of ependymoma: Cancer Cell. 2005;8(4):323-35.10.1016/j.ccr.2005.09.001

2. Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS

Statistical Report: Primary Brain and Other Central Nervous System Tumors

Diagnosed in the United States in 2013-2017: Neuro Oncol. 2020;22(12 Suppl 2):iv1iv96.10.1093/neuonc/noaa200

3. Pajtler KW, Witt H, Sill M, et al. Molecular Classification of Ependymal Tumors

across All CNS Compartments, Histopathological Grades, and Age Groups: Cancer

Cell. 2015;27(5):728-43.10.1016/j.ccell.2015.04.002

4. board WHOcote. Central nervous system tumours: International Agency for

Research on Cancer

World Health Organization [distributor]; 2021. xiii, 568 p. p.

5. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization

Classification of Tumors of the Central Nervous System: a summary: Acta

22

Neuropathol. 2016;131(6):803-20.10.1007/s00401-016-1545-1

6. Ellison DW, Kocak M, Figarella-Branger D, et al. Histopathological grading of

pediatric ependymoma: reproducibility and clinical relevance in European trial

cohorts: J Negat Results Biomed. 2011;10:7.10.1186/1477-5751-10-7

7. Ellison DW, Aldape KD, Capper D, et al. cIMPACT-NOW update 7: advancing the

molecular classification of ependymal tumors: Brain Pathol. 2020;30(5):8636.10.1111/bpa.12866

8. Capper D, Jones DTW, Sill M, et al. DNA methylation-based classification of

central

nervous

system

tumours:

Nature.

2018;555(7697):469-

74.10.1038/nature26000

9. Träger M, Schweizer L, Eilís P, et al. Adult intracranial ependymoma - relevance of

DNA methylation profiling for diagnosis, prognosis and treatment: Neuro Oncol.

2023.10.1093/neuonc/noad030

10. Malgulwar PB, Nambirajan A, Pathak P, et al. C11orf95-RELA fusions and

upregulated NF-KB signalling characterise a subset of aggressive supratentorial

ependymomas that express L1CAM and nestin: J Neurooncol. 2018;138(1):2939.10.1007/s11060-018-2767-y

11. Parker M, Mohankumar KM, Punchihewa C, et al. C11orf95-RELA fusions drive

oncogenic

NF-κB

signalling

in

ependymoma:

Nature.

2014;506(7489):451-

5.10.1038/nature13109

12. Chinnam D, Gupta K, Kiran T, et al. Molecular subgrouping of ependymoma

across three anatomic sites and their prognostic implications: Brain Tumor Pathol.

2022;39(3):151-61.10.1007/s10014-022-00429-2

13. Lim KY, Lee KH, Phi JH, et al. ZFTA-YAP1 fusion-positive ependymoma can

occur

in

the

spinal

cord:

Letter

23

to

the

editor:

Brain

Pathol.

2022;32(1):e13020.10.1111/bpa.13020

14. Zheng T, Ghasemi DR, Okonechnikov K, et al. Cross-Species Genomics Reveals

Oncogenic

Dependencies

in

ZFTA/C11orf95

Fusion-Positive

Supratentorial

Ependymomas: Cancer Discov. 2021;11(9):2230-47.10.1158/2159-8290.Cd-20-0963

15. Tauziède-Espariat A, Siegfried A, Nicaise Y, et al. Supratentorial non-RELA,

ZFTA-fused ependymomas: a comprehensive phenotype genotype correlation

highlighting the number of zinc fingers in ZFTA-NCOA1/2 fusions: Acta Neuropathol

Commun. 2021;9(1):135.10.1186/s40478-021-01238-y

16. Fukuoka K, Kanemura Y, Shofuda T, et al. Significance of molecular classification

of ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are

heterogeneous

group

of

tumors:

Acta

Neuropathol

Commun.

2018;6(1):134.10.1186/s40478-018-0630-1

17. Ritzmann TA, Chapman RJ, Kilday JP, et al. SIOP Ependymoma I: Final results,

long-term follow-up, and molecular analysis of the trial cohort-A BIOMECA

Consortium Study: Neuro Oncol. 2022;24(6):936-48.10.1093/neuonc/noac012

18. Merchant TE, Bendel AE, Sabin ND, et al. Conformal Radiation Therapy for

Pediatric Ependymoma, Chemotherapy for Incompletely Resected Ependymoma,

and Observation for Completely Resected, Supratentorial Ependymoma: J Clin

Oncol. 2019;37(12):974-83.10.1200/jco.18.01765

19. Upadhyaya SA, Robinson GW, Onar-Thomas A, et al. Molecular grouping and

outcomes of young children with newly diagnosed ependymoma treated on the multiinstitutional

SJYC07

trial:

Neuro

Oncol.

2019;21(10):1319-

30.10.1093/neuonc/noz069

20. Jünger ST, Andreiuolo F, Mynarek M, et al. CDKN2A deletion in supratentorial

ependymoma with RELA alteration indicates a dismal prognosis: a retrospective

24

analysis of the HIT ependymoma trial cohort: Acta Neuropathol. 2020;140(3):4057.10.1007/s00401-020-02169-z

21. Witt H, Gramatzki D, Hentschel B, et al. DNA methylation-based classification of

ependymomas in adulthood: implications for diagnosis and treatment: Neuro Oncol.

2018;20(12):1616-24.10.1093/neuonc/noy118

22. Andreiuolo F, Varlet P, Tauziède-Espariat A, et al. Childhood supratentorial

ependymomas with YAP1-MAMLD1 fusion: an entity with characteristic clinical,

radiological,

cytogenetic

and

histopathological

features:

Brain

Pathol.

2019;29(2):205-16.10.1111/bpa.12659

23. Pajtler KW, Wei Y, Okonechnikov K, et al. YAP1 subgroup supratentorial

ependymoma requires TEAD and nuclear factor I-mediated transcriptional

programmes for tumorigenesis: Nat Commun. 2019;10(1):3914.10.1038/s41467019-11884-5

24. Tzaridis T, Milde T, Pajtler KW, et al. Low-dose Actinomycin-D treatment reestablishes the tumoursuppressive function of P53 in RELA-positive ependymoma:

Oncotarget. 2016;7(38):61860-73.10.18632/oncotarget.11452

25. Chapman RJ, Ghasemi DR, Andreiuolo F, et al. Optimising biomarkers for

accurate

ependymoma

International

Clinical

diagnosis,

Trials:

prognostication

BIOMECA

and

study:

stratification

within

Neuro

Oncol.

2023.10.1093/neuonc/noad055

26. Panwalkar P, Clark J, Ramaswamy V, et al. Immunohistochemical analysis of

H3K27me3 demonstrates global reduction in group-A childhood posterior fossa

ependymoma and is a powerful predictor of outcome: Acta Neuropathol.

2017;134(5):705-14.10.1007/s00401-017-1752-4

27. Witt H, Mack SC, Ryzhova M, et al. Delineation of two clinically and molecularly

25

distinct subgroups of posterior fossa ependymoma: Cancer Cell. 2011;20(2):14357.10.1016/j.ccr.2011.07.007

28. Pajtler KW, Wen J, Sill M, et al. Molecular heterogeneity and CXorf67 alterations

in posterior fossa group A (PFA) ependymomas: Acta Neuropathol. 2018;136(2):21126.10.1007/s00401-018-1877-0

29. Baroni LV, Sundaresan L, Heled A, et al. Ultra high-risk PFA ependymoma is

characterized by loss of chromosome 6q: Neuro Oncol. 2021;23(8):136070.10.1093/neuonc/noab034

30. Cavalli FMG, Hübner JM, Sharma T, et al. Heterogeneity within the PF-EPN-B

ependymoma subgroup: Acta Neuropathol. 2018;136(2):227-37.10.1007/s00401018-1888-x

31. Pratt D, Lucas CG, Selvam PP, et al. Recurrent ACVR1 mutations in posterior

fossa ependymoma: Acta Neuropathol. 2022;144(2):373-6.10.1007/s00401-02202435-2

32. Plotkin SR, O'Donnell CC, Curry WT, Bove CM, MacCollin M, Nunes FP. Spinal

ependymomas in neurofibromatosis Type 2: a retrospective analysis of 55 patients: J

Neurosurg Spine. 2011;14(4):543-7.10.3171/2010.11.Spine10350

33. Coy S, Rashid R, Stemmer-Rachamimov A, Santagata S. An update on the CNS

manifestations of neurofibromatosis type 2: Acta Neuropathol. 2020;139(4):64365.10.1007/s00401-019-02029-5

34. Garcia C, Gutmann DH. Nf2/Merlin controls spinal cord neural progenitor

function

in

Rac1/ErbB2-dependent

manner:

PLoS

One.

2014;9(5):e97320.10.1371/journal.pone.0097320

35. Benesch M, Frappaz D, Massimino M. Spinal cord ependymomas in children and

adolescents: Childs Nerv Syst. 2012;28(12):2017-28.10.1007/s00381-012-1908-4

26

36. Oh MC, Tarapore PE, Kim JM, et al. Spinal ependymomas: benefits of extent of

resection for different histological grades: J Clin Neurosci. 2013;20(10):13907.10.1016/j.jocn.2012.12.010

37. Scheil S, Brüderlein S, Eicker M, et al. Low frequency of chromosomal

imbalances in anaplastic ependymomas as detected by comparative genomic

hybridization: Brain Pathol. 2001;11(2):133-43.10.1111/j.1750-3639.2001.tb00386.x

38. Swanson AA, Raghunathan A, Jenkins RB, et al. Spinal Cord Ependymomas

With MYCN Amplification Show Aggressive Clinical Behavior: J Neuropathol Exp

Neurol. 2019;78(9):791-7.10.1093/jnen/nlz064

39. Ghasemi DR, Sill M, Okonechnikov K, et al. MYCN amplification drives an

aggressive form of spinal ependymoma: Acta Neuropathol. 2019;138(6):107589.10.1007/s00401-019-02056-2

40. Buczkowicz P, Hoeman C, Rakopoulos P, et al. Genomic analysis of diffuse

intrinsic pontine gliomas identifies three molecular subgroups and recurrent

activating ACVR1 mutations: Nat Genet. 2014;46(5):451-6.10.1038/ng.2936

41. Korshunov A, Schrimpf D, Ryzhova M, et al. H3-/IDH-wild type pediatric

glioblastoma is comprised of molecularly and prognostically distinct subtypes with

associated

oncogenic

drivers:

Acta

Neuropathol.

2017;134(3):507-

16.10.1007/s00401-017-1710-1

42. Barone G, Anderson J, Pearson AD, Petrie K, Chesler L. New strategies in

neuroblastoma: Therapeutic targeting of MYCN and ALK: Clin Cancer Res.

2013;19(21):5814-21.10.1158/1078-0432.Ccr-13-0680

43. Northcott PA, Jones DT, Kool M, et al. Medulloblastomics: the end of the

beginning: Nat Rev Cancer. 2012;12(12):818-34.10.1038/nrc3410

44. Sonneland PR, Scheithauer BW, Onofrio BM. Myxopapillary ependymoma. A

27

clinicopathologic

and

immunocytochemical

study

of

77

cases:

Cancer.

1985;56(4):883-93.10.1002/1097-0142(19850815)56:4<883::aidcncr2820560431>3.0.co;2-6

45. Warnick RE, Raisanen J, Adornato BT, et al. Intracranial myxopapillary

ependymoma: case report: J Neurooncol. 1993;15(3):251-6.10.1007/bf01050071

46. Chakraborti S, Govindan A, Alapatt JP, Radhakrishnan M, Santosh V. Primary

myxopapillary ependymoma of the fourth ventricle with cartilaginous metaplasia: a

case report and review of the literature: Brain Tumor Pathol. 2012;29(1):2530.10.1007/s10014-011-0059-8

47. Ralte AM, Rao S, Sharma MC, Suri A, Gaikwad S, Sarkar C. Myxopapillary

ependymoma of the temporal lobe--report of a rare case of temporal lobe epilepsy:

Clin Neuropathol. 2004;23(2):53-8

48. Bates JE, Choi G, Milano MT. Myxopapillary ependymoma: a SEER analysis of

epidemiology and outcomes: J Neurooncol. 2016;129(2):251-8.10.1007/s11060-0162167-0

49. Nguyen HS, Doan N, Gelsomino M, Shabani S. Intracranial Subependymoma: A

SEER

Analysis

2004-2013:

World

Neurosurg.

2017;101:599-

605.10.1016/j.wneu.2017.02.019

50. Fischer SB, Attenhofer M, Gultekin SH, Ross DA, Heinimann K. TRPS1 gene

alterations

in

human

subependymoma:

Neurooncol.

2017;134(1):133-

8.10.1007/s11060-017-2496-7

51. Robertson PL, Zeltzer PM, Boyett JM, et al. Survival and prognostic factors

following radiation therapy and chemotherapy for ependymomas in children: a report

of

the

Children's

Cancer

Group:

703.10.3171/jns.1998.88.4.0695

28

Neurosurg.

1998;88(4):695-

52. Timmermann B, Kortmann RD, Kühl J, et al. Combined postoperative irradiation

and chemotherapy for anaplastic ependymomas in childhood: results of the German

prospective trials HIT 88/89 and HIT 91: Int J Radiat Oncol Biol Phys.

2000;46(2):287-95.10.1016/s0360-3016(99)00414-9

53. Massimino M, Gandola L, Giangaspero F, et al. Hyperfractionated radiotherapy

and chemotherapy for childhood ependymoma: final results of the first prospective

AIEOP (Associazione Italiana di Ematologia-Oncologia Pediatrica) study: Int J Radiat

Oncol Biol Phys. 2004;58(5):1336-45.10.1016/j.ijrobp.2003.08.030

54. Garvin JH, Jr., Selch MT, Holmes E, et al. Phase II study of pre-irradiation

chemotherapy for childhood intracranial ependymoma. Children's Cancer Group

protocol 9942: a report from the Children's Oncology Group: Pediatr Blood Cancer.

2012;59(7):1183-9.10.1002/pbc.24274

55. Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA. Conformal

radiotherapy after surgery for paediatric ependymoma: a prospective study: Lancet

Oncol. 2009;10(3):258-66.10.1016/s1470-2045(08)70342-5

56. Massimino M, Miceli R, Giangaspero F, et al. Final results of the second

prospective AIEOP protocol for pediatric intracranial ependymoma: Neuro Oncol.

2016;18(10):1451-60.10.1093/neuonc/now108

57. Millward CP, Mallucci C, Jaspan T, et al. Assessing 'second-look' tumour

resectability in childhood posterior fossa ependymoma-a centralised review panel

and staging tool for future studies: Childs Nerv Syst. 2016;32(11):218996.10.1007/s00381-016-3225-9

58. Massimino M, Solero CL, Garrè ML, et al. Second-look surgery for ependymoma:

the

Italian

experience:

Neurosurg

50.10.3171/2011.6.Peds1142

29

Pediatr.

2011;8(3):246-

59. Ramaswamy V, Hielscher T, Mack SC, et al. Therapeutic Impact of Cytoreductive

Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A

Retrospective

Multicohort

Analysis:

Clin

Oncol.

2016;34(21):2468-

77.10.1200/jco.2015.65.7825

60. Metellus P, Barrie M, Figarella-Branger D, et al. Multicentric French study on

adult intracranial ependymomas: prognostic factors analysis and therapeutic

considerations from a cohort of 152 patients: Brain. 2007;130(Pt 5):133849.10.1093/brain/awm046

61. Korshunov A, Golanov A, Sycheva R, Timirgaz V. The histologic grade is a main

prognostic factor for patients with intracranial ependymomas treated in the

microneurosurgical era: an analysis of 258 patients: Cancer. 2004;100(6):12307.10.1002/cncr.20075

62. Rodríguez D, Cheung MC, Housri N, Quinones-Hinojosa A, Camphausen K,

Koniaris LG. Outcomes of malignant CNS ependymomas: an examination of 2408

cases through the Surveillance, Epidemiology, and End Results (SEER) database

(1973-2005): J Surg Res. 2009;156(2):340-51.10.1016/j.jss.2009.04.024

63. Rudà R, Reifenberger G, Frappaz D, et al. EANO guidelines for the diagnosis

and

treatment

of

ependymal

tumors:

Neuro

Oncol.

2018;20(4):445-

56.10.1093/neuonc/nox166

64. Merchant TE, Sharma S, Xiong X, Wu S, Conklin H. Effect of cerebellum

radiation

dosimetry

ependymoma:

Int

on

cognitive

Radiat

outcomes

in

Oncol

Biol

children

Phys.

with

infratentorial

2014;90(3):547-

53.10.1016/j.ijrobp.2014.06.043

65. Conklin HM, Li C, Xiong X, Ogg RJ, Merchant TE. Predicting change in

academic abilities after conformal radiation therapy for localized ependymoma: J Clin

30

Oncol. 2008;26(24):3965-70.10.1200/jco.2007.15.9970

66. Macdonald SM, Sethi R, Lavally B, et al. Proton radiotherapy for pediatric central

nervous system ependymoma: clinical outcomes for 70 patients: Neuro Oncol.

2013;15(11):1552-9.10.1093/neuonc/not121

67. Ghia AJ, Mahajan A, Allen PK, et al. Supratentorial gross-totally resected nonanaplastic ependymoma: population based patterns of care and outcomes analysis:

J Neurooncol. 2013;115(3):513-20.10.1007/s11060-013-1254-8

68. Nuño M, Yu JJ, Varshneya K, et al. Treatment and survival of supratentorial and

posterior

fossa

ependymomas

in

adults:

Clin

Neurosci.

2016;28:24-

30.10.1016/j.jocn.2015.11.014

69. Bouffet E, Hawkins CE, Ballourah W, et al. Survival benefit for pediatric patients

with recurrent ependymoma treated with reirradiation: Int J Radiat Oncol Biol Phys.

2012;83(5):1541-8.10.1016/j.ijrobp.2011.10.039

70. Kano H, Yang HC, Kondziolka D, et al. Stereotactic radiosurgery for pediatric

recurrent

intracranial

ependymomas:

Neurosurg

Pediatr.

2010;6(5):417-

23.10.3171/2010.8.Peds10252

71. Hoffman LM, Plimpton SR, Foreman NK, et al. Fractionated stereotactic

radiosurgery for recurrent ependymoma in children: J Neurooncol. 2014;116(1):10711.10.1007/s11060-013-1259-3

72. Eaton BR, Chowdhry V, Weaver K, et al. Use of proton therapy for re-irradiation

in

pediatric

intracranial

ependymoma:

Radiother

Oncol.

2015;116(2):301-

8.10.1016/j.radonc.2015.07.023

73. Adolph JE, Fleischhack G, Mikasch R, et al. Local and systemic therapy of

recurrent ependymoma in children and adolescents: short- and long-term results of

the

E-HIT-REZ

2005

study:

Neuro

31

Oncol.

2021;23(6):1012-

23.10.1093/neuonc/noaa276

74. Komori K, Yanagisawa R, Miyairi Y, et al. Temozolomide Treatment for Pediatric

Refractory Anaplastic Ependymoma with Low MGMT Protein Expression: Pediatr

Blood Cancer. 2016;63(1):152-5.10.1002/pbc.25696

75. Rudà R, Bosa C, Magistrello M, et al. Temozolomide as salvage treatment for

recurrent intracranial ependymomas of the adult: a retrospective study: Neuro Oncol.

2016;18(2):261-8.10.1093/neuonc/nov167

76. Gilbert MR, Yuan Y, Wu J, et al. A phase II study of dose-dense temozolomide

and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and

spinal

cord

ependymoma:

Neuro

Oncol.

2021;23(3):468-

77.10.1093/neuonc/noaa240

77. Robison NJ, Campigotto F, Chi SN, et al. A phase II trial of a multi-agent oral

antiangiogenic (metronomic) regimen in children with recurrent or progressive

cancer: Pediatr Blood Cancer. 2014;61(4):636-42.10.1002/pbc.24794

78. Mendrzyk F, Korshunov A, Benner A, et al. Identification of gains on 1q and

epidermal growth factor receptor overexpression as independent prognostic markers

in

intracranial

ependymoma:

Clin

Cancer

Res.

2006;12(7

Pt

1):2070-

9.10.1158/1078-0432.Ccr-05-2363

79. Gilbertson RJ, Bentley L, Hernan R, et al. ERBB receptor signaling promotes

ependymoma cell proliferation and represents a potential novel therapeutic target for

this disease: Clin Cancer Res. 2002;8(10):3054-64

80. Friedrich C, von Bueren AO, Kolevatova L, et al. Epidermal growth factor

receptor overexpression is common and not correlated to gene copy number in

ependymoma: Childs Nerv Syst. 2016;32(2):281-90.10.1007/s00381-015-2981-2

81. Jakacki RI, Foley MA, Horan J, et al. Single-agent erlotinib versus oral etoposide

32

in patients with recurrent or refractory pediatric ependymoma: a randomized openlabel study: J Neurooncol. 2016;129(1):131-8.10.1007/s11060-016-2155-4

82. Wetmore C, Daryani VM, Billups CA, et al. Phase II evaluation of sunitinib in the

treatment of recurrent or refractory high-grade glioma or ependymoma in children: a

children's Oncology Group Study ACNS1021: Cancer Med. 2016;5(7):141624.10.1002/cam4.713

83. Cash T, Fox E, Liu X, et al. A phase 1 study of prexasertib (LY2606368), a

CHK1/2 inhibitor, in pediatric patients with recurrent or refractory solid tumors,

including CNS tumors: A report from the Children's Oncology Group Pediatric Early

Phase

Clinical

Trials

Network

(ADVL1515):

Pediatr

Blood

Cancer.

2021;68(9):e29065.10.1002/pbc.29065

84. Bukowinski A, Chang B, Reid JM, et al. A phase 1 study of entinostat in children

and adolescents with recurrent or refractory solid tumors, including CNS tumors:

Trial ADVL1513, Pediatric Early Phase-Clinical Trial Network (PEP-CTN): Pediatr

Blood Cancer. 2021;68(4):e28892.10.1002/pbc.28892

85. Qayed M, Cash T, Tighiouart M, et al. A phase I study of sirolimus in combination

with metronomic therapy (CHOAnome) in children with recurrent or refractory solid

and brain tumors: Pediatr Blood Cancer. 2020;67(4):e28134.10.1002/pbc.28134

86. Cole KA, Pal S, Kudgus RA, et al. Phase I Clinical Trial of the Wee1 Inhibitor

Adavosertib (AZD1775) with Irinotecan in Children with Relapsed Solid Tumors: A

COG Phase I Consortium Report (ADVL1312): Clin Cancer Res. 2020;26(6):12139.10.1158/1078-0432.Ccr-19-3470

87. Sandberg DI, Yu B, Patel R, et al. Infusion of 5-Azacytidine (5-AZA) into the

fourth ventricle or resection cavity in children with recurrent posterior Fossa

Ependymoma:

pilot

clinical

trial:

33

Neurooncol.

2019;141(2):449-

57.10.1007/s11060-018-03055-1

88. Pasqualini C, Rubino J, Brard C, et al. Phase II and biomarker study of

programmed

cell

death

protein

inhibitor

nivolumab

and

metronomic

cyclophosphamide in paediatric relapsed/refractory solid tumours: Arm G of AcSéESMART, a trial of the European Innovative Therapies for Children With Cancer

Consortium: Eur J Cancer. 2021;150:53-62.10.1016/j.ejca.2021.03.032

89. Cacciotti C, Choi J, Alexandrescu S, et al. Immune checkpoint inhibition for

pediatric patients with recurrent/refractory CNS tumors: a single institution

experience: J Neurooncol. 2020;149(1):113-22.10.1007/s11060-020-03578-6

90. Khatua S, Cooper LJN, Sandberg DI, et al. Phase I study of intraventricular

infusions of autologous ex vivo expanded NK cells in children with recurrent

medulloblastoma

and

ependymoma:

Neuro

Oncol.

2020;22(8):1214-

25.10.1093/neuonc/noaa047

91. Kieran MW, Goumnerova L, Manley P, et al. Phase I study of gene-mediated

cytotoxic immunotherapy with AdV-tk as adjuvant to surgery and radiation for

pediatric

malignant

glioma

and

recurrent

2019;21(4):537-46.10.1093/neuonc/noy202

34

ependymoma:

Neuro

Oncol.

...